Diagnosis and Treatment > Signs and Symptoms
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Summary
POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein and Skin changes) is a rare multisystemic disease. Clinical presentation is variable, the only mandatory criteria being polyneuropathy and monoclonal gammapathy in association with one major and one minor criterion. Primary adrenal insufficiency is rarely reported. We describe a case of a 33-year-old patient, in whom the presenting symptoms were mandibular mass, chronic sensory-motor peripheral polyneuropathy and adrenal insufficiency. The laboratory evaluation revealed thrombocytosis, severe hyperkalemia with normal renal function, normal protein electrophoresis and negative serum immunofixation for monoclonal protein. Endocrinologic laboratory work-up confirmed Addison’s disease and revealed subclinical primary hypothyroidism. Thoracic abdominal CT showed hepatosplenomegaly, multiple sclerotic lesions in thoracic vertebra and ribs. The histopathologic examination of the mandibular mass was nondiagnostic. Bone marrow biopsy revealed plasma cell dyscrasia and confirmed POEMS syndrome. Axillary lymphadenopathy biopsy: Castleman’s disease. Gluco-mineralocorticoid substitution and levothyroxine therapy were started with clinical improvement. Autologous hematopoietic cell transplantation (HCT) was planned, cyclophosphamide induction was started. Meanwhile the patient suffered two ischemic strokes which resulted in aphasia and hemiparesis. Cerebral angiography revealed vascular lesions compatible with vasculitis and stenosis of two cerebral arteries. The patient deceased 14 months after the diagnosis. The young age at presentation, multiplicity of manifestations and difficulties in investigation along with the absence of serum monoclonal protein made the diagnosis challenging. We report this case to highlight the need to consider POEMS syndrome in differential diagnosis of peripheral neuropathy in association with endocrine abnormalities even in young patients.
Learning points:
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POEMS syndrome is considered a ‘low tumor burden disease’ and the monoclonal protein in 15% of cases is not found by immunofixation.
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Neuropathy is the dominant characteristic of POEMS syndrome and it is peripheral, ascending, symmetric and affecting both sensation and motor function.
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Endocrinopathies are a frequent feature of POEMS syndrome, but the cause is unknown.
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The most common endocrinopathies are hypogonadism, primary hypothyroidism and abnormalities in glucose metabolism.
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There is no standard therapy; however, patients with disseminated bone marrow involvement are treated with chemotherapy with or without HCT.
Division of Experimental Medicine, Faculty of Medicine, Imperial College London, Hammersmith Campus, London, UK
Division of Translational and Systems Medicine, Warwick Medical School, University of Warwick, Coventry, UK
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Department of Clinical Biochemistry and Histopathology, Coventry and Warwickshire, Pathology Service, UHCW NHS Trust, Coventry, UK
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Division of Translational and Systems Medicine, Warwick Medical School, University of Warwick, Coventry, UK
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Summary
We report the case of a 70-year-old previously healthy female who presented acutely to the Accident and Emergency department with left-sided vasomotor symptoms including reduced muscle tone, weakness upon walking and slurred speech. Physical examination confirmed hemiparesis with VIIth nerve palsy and profound hepatomegaly. A random glucose was low at 1.7 mmol/l, which upon correction resolved her symptoms. In hindsight, the patient recalled having had similar episodes periodically over the past 3 months to which she did not give much attention. While hospitalized, she continued having episodes of symptomatic hypoglycaemia during most nights, requiring treatment with i.v. dextrose and/or glucagon. Blood tests including insulin and C-peptide were invariably suppressed, in correlation with low glucose. A Synacthen stimulation test was normal (Cort (0′) 390 nmol/l, Cort (30′) 773 nmol/l). A computed tomography scan showed multiple lobulated masses in the abdomen, liver and pelvis. An ultrasound guided biopsy of one of the pelvic masses was performed. Immunohistochemistry supported the diagnosis of a gastrointestinal stromal tumour (GIST) positive for CD34 and CD117. A diagnosis of a non islet cell tumour hypoglycaemia (NICTH) secondary to an IGF2 secreting GIST was confirmed with further biochemical investigations (IGF2=96.5 nmol/l; IGF2:IGF1 ratio 18.9, ULN <10). Treatment with growth hormone resolved the patient's hypoglycaemic symptoms and subsequent targeted therapy with Imatinib was successful in controlling disease progression over an 8-year observation period.
Learning points
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NICTH can be a rare complication of GISTs that may manifest with severe hypoglycaemia and neuroglucopenic symptoms.
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NICTH can masquerade as other pathologies thus causing diagnostic confusion.
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Histological confirmation of GIST induced NICTH and exclusion of other conditions causing hypoglycaemia is essential.
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Mutational analysis of GISTs should be carried out in all cases as it guides treatment decision.
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Tailored management of hypoglycaemia, in this case using growth hormone and targeted cyto-reductive therapy, minimizes the risk of possible life-threatening complications.
